1. Field of the Invention
The present invention relates to new ergoline derivatives and to the process for their preparation. More particularly the present invention relates to the preparation of compounds of general formula I ##STR1## where R.sub.1 can be H or CH.sub.3, R.sub.2 can be H or OCH.sub.3, R.sub.3 can be H, CH.sub.3, OH, CH.sub.3 O, CH.sub.3 S, Cl, or Br, and X can be NH or S. The products of the present invention are formed by reacting the appropriate 8.beta.-tosylmethyl ergoline II, where R.sub.1 and R.sub.2 have the above reported meanings with a compound of formula III in which X is as above defined, namely with the sodium derivative of the appropriate amino or mercaptopyridazine where R.sub.3 has the above reported meaning, in a dipolar aprotic solvent such as dimethyl sulfoxide, dimethylformamide, hexamethylphosphotriamide at a temperature of from 30.degree. to 120.degree. C. for 1 to 6 hours. The compounds are isolated as free bases or as salts of pharmaceutically acceptable acids. The products of the present invention show a pharmacological activity hitherto unreported for ergoline derivatives, namely they are highly effective in protecting mice from the effects of administration of an otherwise lethal dose of amphetamine.
2. Description of the Prior Art
In 1957 L. Lasagna and W. P. McCann (Science, 125, 1241) reported that "tranquilizing" drugs, and particularly chlorpromazine, clearly reduce the amphetamine toxicity in aggregated mice. Subsequently many authors (C. D. Proctor et al., Arch. Int. Pharmacodyn., 1966, 163, 79; J. R. Boissier and P. Simon, Therapie, 1966, 21, 1491; D. E. Smith et al., Tox. Appl. Pharm., 1967, 10, 402; R. Cahen, C.R.S.B., 1968, 161, 2441) confirmed the activity of other neuroleptics in this test. As far as we known this activity was never described for molecules belonging to the ergoline group.